On March 5, 2026, the U.S. FDA approved teclistamab (Tecvayli), a BCMA×CD3 bispecific antibody, in combination with daratumumab hyaluronidase-fihj for adults with relapsed or refractory multiple myeloma (RRMM) who have received at least one prior line of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD).
On the same day, the FDA also converted teclistamab monotherapy from accelerated approval (granted in 2022) to traditional approval for adults with RRMM who have received at least four prior lines of therapy including a PI, an IMiD, and an anti-CD38 monoclonal antibody.
Regulatory summary and eligible patient population
Indication and prior-therapy requirements (treatment line)
Combination indication: adult RRMM with ≥1 prior line of therapy including a PI and an IMiD.
Monotherapy positioning (converted to traditional approval): adult RRMM with ≥4 prior lines including a PI, an IMiD, and an anti-CD38 monoclonal antibody.
Drug class and therapeutic concept (BCMA×CD3 bispecific antibody)
Teclistamab engages BCMA on myeloma cells and CD3 on T cells to redirect T-cell cytotoxicity toward tumor cells. The approval highlights a strategy of intensifying anti-myeloma activity by combining T-cell redirection with an anti-CD38 backbone (subcutaneous daratumumab with hyaluronidase).
Key trial MajesTEC-3: design and efficacy outcomes
Trial design and control regimens (DPd or DVd)
Efficacy was evaluated in MajesTEC-3 (NCT05083169), a randomized, open-label, multicenter trial. In total, 587 patients were randomized to teclistamab plus daratumumab hyaluronidase-fihj (n=291) or investigator’s choice control (n=296): daratumumab hyaluronidase-fihj + pomalidomide + dexamethasone (DPd) or daratumumab hyaluronidase-fihj + bortezomib + dexamethasone (DVd).
PFS and OS (hazard ratio: PFS 0.17, OS 0.46)
The primary endpoint was progression-free survival (PFS) by independent review committee assessment using IMWG 2016 criteria. Median PFS was not reached in the teclistamab combination arm and 18.1 months in the control arm (hazard ratio 0.17; p<0.0001). Overall survival (OS) was an additional endpoint, with a reported hazard ratio of 0.46 (p<0.0001).
Practically, these data suggest a substantial improvement in disease control (at least by PFS) in the relapsed setting. As with many open-label studies, real-world adoption will still require careful patient selection and operational readiness for toxicity management.
Safety profile and clinical considerations
Boxed Warning: CRS and neurologic toxicity (including ICANS)
Tecvayli prescribing information includes a Boxed Warning for life-threatening or fatal cytokine release syndrome (CRS) and neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS). Tecvayli is available only through a restricted REMS program (Tecvayli-Talvey REMS).
Common adverse reactions with the combination (infections, hypogammaglobulinemia, etc.)
Beyond CRS, commonly reported adverse reactions for the combination include hypogammaglobulinemia, upper respiratory tract infection, cough, diarrhea, musculoskeletal pain, COVID-19, pneumonia, injection site reaction, fatigue, pyrexia, headache, nausea, gastroenteritis, and decreased weight.
In practice, infection prevention/monitoring and structured CRS/ICANS recognition and management pathways are central to safe delivery of T-cell redirecting therapies.
Regulatory context: Priority Review, Project Orbis, RTOR
CNPV pilot, Priority Review, Breakthrough/Orphan designations
This application was reviewed under the FDA Commissioner’s National Priority Review Voucher (CNPV) pilot program. The review was conducted as a Priority Review, and teclistamab received Breakthrough Therapy designation and Orphan Drug designation.
Project Orbis and Real-Time Oncology Review (RTOR)
The review was conducted under Project Orbis (FDA Oncology Center of Excellence), enabling concurrent submission and review with international partners. For this review, FDA collaborated with Health Canada and Switzerland’s Swissmedic. The submission also leveraged the Real-Time Oncology Review (RTOR) pilot and the Assessment Aid to streamline data submission and assessment.
Clinical positioning and outlook (treatment sequencing in multiple myeloma)
Versus DPd/DVd: potential impact on relapsed-setting choices
By using DPd or DVd as pragmatic comparators, MajesTEC-3 speaks directly to real-world relapsed-setting decisions. The magnitude of PFS benefit suggests that adding teclistamab to a daratumumab backbone may meaningfully reshape options for selected patients, balanced against CRS/ICANS risk and infection burden.
Meaning of monotherapy conversion to traditional approval: maturing evidence and broader use
The conversion of teclistamab monotherapy from accelerated to traditional approval signals maturing evidence and supports a more established role for the agent. As combination strategies expand, the next frontier will be optimizing sequencing across immunotherapies and other advanced modalities.
Sources
- AACR FDA Approval Alert (2026-03-05): teclistamab + daratumumab hyaluronidase-fihj in RRMM
- Trial: MajesTEC-3 (NCT05083169)
- Prescribing information: Drugs@FDA (Tecvayli) to be posted
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